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104. Fabry Disease Therapy: State-of-the-Art and Current Challenges.

Author

Azevedo, Olga, Gago, Miguel Fernandes, Miltenberger-Miltenyi, Gabriel, Sousa, Nuno, and Cunha, Damião

Subjects
*ANGIOKERATOMA corporis diffusum, *GALACTOSIDASES, *LYSOSOMAL storage diseases, *GENE therapy, *CLINICAL pathology, *CLINICAL trials
Abstract

Fabry disease (FD) is a lysosomal storage disorder caused by mutations of the GLA gene that lead to a deficiency of the enzymatic activity of α-galactosidase A. Available therapies for FD include enzyme replacement therapy (ERT) (agalsidase alfa and agalsidase beta) and the chaperone migalastat. Despite the large body of literature published about ERT over the years, many issues remain unresolved, such as the optimal dose, the best timing to start therapy, and the clinical impact of anti-drug antibodies. Migalastat was recently approved for FD patients with amenable GLA mutations; however, recent studies have raised concerns that "in vitro" amenability may not always reflect "in vivo" amenability, and some findings on real-life studies have contrasted with the results of the pivotal clinical trials. Moreover, both FD specific therapies present limitations, and the attempt to correct the enzymatic deficiency, either by enzyme exogenous administration or enzyme stabilization with a chaperone, has not shown to be able to fully revert FD pathology and clinical manifestations. Therefore, several new therapies are under research, including new forms of ERT, substrate reduction therapy, mRNA therapy, and gene therapy. In this review, we provide an overview of the state-of-the-art on the currently approved and emerging new therapies for adult patients with FD. [ABSTRACT FROM AUTHOR]

Published
2021
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105. Correlación genotipo-fenotipo en miocardiopatía hipertrófica: un estudio multicéntrico en Portugal y España sobre la variante p.Arg21Leu de TPM1

Author

Lamounier Junior, Arsonval, Guitián González, Alba, Rodríguez Vilela, Alejandro, Repáraz Andrade, Alfredo, Rubio Alcaide, Álvaro, Berta Sousa, Ana, Benito López, Carmen, Alonso García, Diego, Fernández Ferro, Germán, Cruz, Inês, Cárdenas Reyes, Ivonne Johana, Salazar-Mendiguchía García, Joel, Larrañaga-Moreira, José María, Ochoa, Juan Pablo, Palomino-Doza, Julián, de la Higuera Romero, Luis, Nicolás Cicerchia, Marcos, Restrepo Córdoba, María Alejandra, Peña-Peña, María Luisa, Noël Brögger, Maria, Loureiro, Marilia, Mogollón Jiménez, María Victoria, Bilbao Quesada, Raquel, Franco Gutiérrez, Raúl, García Hernández, Soledad, Ripoll-Vera, Tomás, Fernández, Xusto, Azevedo, Olga, García Pavía, Pablo, Lopes, Luis R., Ortiz, Martín, Brito, Dulce, Barriales-Villa, Roberto, and Monserrat Iglesias, Lorenzo

Abstract

TPM1es uno de los principales genes en la miocardiopatía hipertrófica (MCH). La información clínica sobre portadores es relativamente escasa, lo cual limita la interpretación de los estudios genéticos. Nuestro objetivo es establecer la correlación genotipo-fenotipo de la variante p.Arg21Leu de TPM1en una serie de familias.

Published
2021
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106. Não compactação do ventrículo esquerdo associada a mutação no gene MYH7: mutação conhecida, fenótipo alternativo!

Author

Oliveira, Margarida, Azevedo, Olga, Faria, Bebiana, Hafe, Pedro von, Dias, Geraldo, Faria, Ricardo, Sanfins, Victor, Lourenço, Mário, Miltenberger-Miltenyi, Gabriel, and Lourenço, António

Abstract

Left ventricular noncompaction (LVNC) is a genetically heterogeneous cardiomyopathy, with familial and sporadic forms, but genetic testing only identifies a pathogenic mutation in a minority of cases. The main complications are heart failure, embolism and dysrhythmias. Herein we report a familial case of LVNC associated with a mutation in the MYH7gene and review the literature regarding controversies in LVNC. A 50-year-old woman was referred to the cardiology clinic for palpitations. She underwent echocardiography and cardiac magnetic resonance imaging that revealed mild left ventricular systolic dysfunction and LVNC criteria. She had several episodes of non-sustained ventricular tachycardia and received an implantable cardioverter-defibrillator (ICD). Genetic testing revealed the c.1003G>C (p.Ala335Pro) mutation in the MYH7gene. Familial screening showed clear genotype-phenotype cosegregation, which provided strong evidence for the pathogenic role of this mutation. To the best of our knowledge, this is the first report of LVNC associated with the p.Ala335Pro mutation in the MYH7gene. This mutation has been described in hypertrophic cardiomyopathy, suggesting that the same pathogenic sarcomere mutation may be associated with different cardiomyopathies. This case also highlights the current difficulties regarding decisions on ICD implantation for primary prevention of sudden cardiac death in LVNC.

Published
2021
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107. Chegou a hora do recreio! O recreio: espaço de construção de culturas da infância

Author

Azevedo, Olga Maria Queirós de, Fernandes, Natália, and Universidade do Minho

Subjects
Recreio, Ciências da Educação [Ciências Sociais], Culturas da infância, 37.015.4, Childhood cultures, Jogos, Playground, Brincadeiras, Games, 372.3, Ciências Sociais::Ciências da Educação, Playtime
Abstract

Dissertação de mestrado em Estudos da Criança (área de especialização em Associativismo e Animação Sócio-Cultural), Esta proposta de investigação tem como enfoque principal compreender como é que as crianças constroem as culturas identitárias da sua geração no espaço e tempo de recreio. Para tal foram tidas em conta as ações e interações que edificam com os seus pares, as brincadeiras que reinventam e promovem e o modo como se organizam. Para chegarmos a essa compreensão optamos por uma investigação de cariz etnográfica interpretativo e participativo. A recolha de dados foi realizada através da observação participante no tempo e espaço de recreio de um jardim-de-infância público. Os grupos de crianças são heterogéneos e com idades entre os 3 e os 6 anos de idade. Através das suas vozes e das suas ações foi mais fácil compreender as suas interpretações, intenções e culturas. Ainda, para dar voz às crianças, foi constituído um grupo focal. Deste grupo fizeram parte as 16 crianças de 5/6 anos de idade de ambas as salas. Nestes debates alargados as crianças partilharam e explanaram brincadeiras, jogos e descobertas realizadas, assim como conflitos que surgiram neste tempo e espaço de recreio, cenário desta investigação. Fizeram parte da investigação registos realizados em conselho de grupo semanal, onde as crianças expressaram o que mais gostavam e o que menos gostavam do recreio. Pudemos observar que as crianças inventam e reinventam brincadeiras, de acordo com as suas vivências e experiências sociais. Que ao espaço e materiais, nessas brincadeiras, podem ser atribuídos diferentes significados, conforme a necessidade para dar continuidade às mesmas ou para que se possam realizar. Compreendemos que as crianças constroem e seguem regras para brincar, mesmo quando aos olhos do adulto o caos parece instalado. Nesta investigação fica também a reflexão sobre a importância deste espaço na vida das crianças. Uma vida enclausurada em casa e na escola onde escasseiam momentos e companheiros de brincadeiras. Deste modo o recreio deve surgir como o espaço das e para as crianças, onde o adulto deve ser o menos invasivo possível de modo a facilitar a construção das culturas da infância., This research proposal has its main focus on understanding how children build their generational cultural identities in the playground. For this, actions and interactions among their peers were taken into account and also the way they organize themselves in the games they reinvent and promote. In order to do this, we develop an ethnographic research with an interpretative and participatory focus. All the data was collected during their recess breaks at a public preschool. The group had boys and girls ranging from 3 to 6 years of age. The research data was done by direct observation involving all the 38 children. Through their actions and voices it was easier to understand their interpretations, intentions and cultures. In order to consider children´s voices and opinions, we developed a focus group that was organized with 16 children from 5 and 6 years old, from both classrooms. These debates involved children´s discussions about things that occurred at the playground, by sharing and explaining games and the outcomes, as well as the conflicts which occurred during this time and space. We also used data from the weekly group meeting, which allowed us to acknowledge what children liked most and least in the playground. We can conclude that children invent and reinvent games according to their backgrounds and social experiences. They give different meanings to the space and materials in these games, considering the way how they were developed. We can also conclude that children build and follow rules to play, even when it seems like chaos in an adult point of view. In this research, we also want to highlight the importance of this space in children’s lives. An institutionalized life, confined at home, on one hands, and on the other hand, at school, don’t allow children to play with their peers. As such, the recess emerges as a space for and owned by children, where the adult has to play the role of less invasive in order to allow that children can be more active in the development of their cultures and also in the development of their identities.

108. Abstracts

Author

Treibel, Thomas A., Fridman, Yaron, Hackman, Brianne, Kadakkal, Ajay, Sayeed, Aatif, Maanja, Maren, Daya, Hussein Abu, Moon, James C., Wong, Timothy C., Schelbert, Erik B., Duca, Franz, Kammerlander, Andreas A., Zotter-Tufaro, Caroline, Aschauer, Stefan, Bonderman, Diana, Mascherbauer, Julia, Schwitter, Juerg, Beigelman-Aubry, Catherine, Peguret, Nicolas, Stuber, Matthias, Delacoste, Jean, Belmondo, Bastien, Lovis, Alban, Simons, Julien, Long, Olivier, Grant, Kathleen, Berchier, Gregoire, Rohner, Chantal, Bonanno, Gabriele, Coppo, Simone, Ozsahin, Esat-Mahmut, Qanadli, Salah, Meuli, Reto, Bourhis, Jean, Ide, Seiko, Riesenkampff, Eugenie, Chiasson, David, Dipchand, Anne I., Kantor, Paul F., Chaturvedi, Rajiv R., Yoo, Shi-Joon, Grosse-Wortmann, Lars, Sandrini, C., Aquaro, GD, De Marchi, D, Ait Ali, L, Khraiche, D, Boddaert, N, Bonnet, D, Raimondi, F, Fridman, Yaron, Hackman, Brianne E., Kadakkal, Ajay, Daya, Hussein Abu, Wong, Timothy C., Schelbert, Erik B., Angela, Susana, Alberto, Cipriani, Manuel, De Lazzari, Federico, Marin, Francesca, Prevedello, Bendetta, Giorgi, Giorgio, De Conti, Giuseppe, Tarantini, Luisa, Cacciavillani, Emanuele, Bertaglia, Domenico, Corrado, Sabino, Iliceto, Martina, Perazzolo Marra, Camaioni, Claudia, Morlon, Lucas, Vergé, Marie-Philippe, Jais, Pierre, Roudaut, Raymond, Laurent, Francois, Lafitte, Stéphane, Cochet, Hubert, Réant, Patricia, Bohnen, S., Radunski, U. K., Lund, G. K., Senel, M., Avanesov, M., Tahir, E., Stehning, C., Adam, G., Blankenberg, S., Muellerleile, K., Khanji, Mohammed Y., Balawon, Armida, Boubertakh, Redha, Petersen, Steffen E, Hilbert, Sebastian, Spampinato, Ricardo, Oebel, Sabrina, Hindricks, Gerhard, Bollmann, Andreas, Jahnke, Cosima, Paetsch, Ingo, Goetschalckx, K., Bogaert, J., Desmet, W., Toth, A., Merkely, B., Janssens, S., Claus, P., Calvieri, C., Preda, M. B., Perfetti, A., Valaperta, R., Secchi, F., Fedele, F., Martelli, F., Lombardi, M., Reinstadler, Sebastian J., Eitel, Charlotte, Fuernau, Georg, de Waha, Suzanne, Desch, Steffen, Mende, Meinhard, Metzler, Bernhard, Schuler, Gerhard, Thiele, Holger, Eitel, Ingo, Maestrini, Viviana, Mun, Hong Cheang, Kotwinski, Paul, Rosmini, Stefania, Sanders, Julie, Lloyd, Guy, Dudley, J. Pennell, Kellman, Peter, Hugh, E. Montgomery, Manisty, Charlotte, James, C. Moon, James, S., Waterhouse, D.F., Murphy, T.M., Kenny, C., O'Hanlon, R., Bastiaenen, Rachel, Cox, Andrew T., Wijeyeratne, Yanushi, Colbeck, Nicholas, Pakroo, Nadia, Ahmed, Hammad, Bunce, Nick, Anderson, Lisa, Prasad, Sanjay, Sharma, Sanjay, Behr, Elijah R., Reid, A. B., Miller, C., Jovanovic, A., Woolfson, P., Abidin, N., Schmitt, M., Amadu, A.M., Rodrigues, J.C.L., Dastidar, A. Ghosh, Baritussio, A., Lawton, C., Venuti, G., Meloni, G.B., Conti, M., Bucciarelli-Ducci, C., Pontone, Gianluca, Andreini, Daniele, SoLbiati, Anna, Guglielmo, Marco, Mushtaq, Saima, Baggiano, Andrea, Beltrama, Virginia, Rota, Cristina, Guaricci, Andrea I., Pepi, Mauro, Wang, Yufei, Joannic, David, Juillion, Patrick, Delassus, P., Monnet, Aurélien, Lalande, Alain, Fontaine, Jean-Francois, Zweerink, A, Allaart, CP, Wu, L, Kuijer, JPA, Beek, AM, Croisille, P, Clarysse, P, van Rossum, AC, Nijveldt, R, Bulluck, Heerajnarain, Rosmini, Stefania, Abdel-Gadir, Amna, Bhuva, Anish, Treibel, Thomas A, White, Steven K, Hammond-Haley, Matthew, Sirker, Alex, Herrey, Anna, Manisty, Charlotte, Yellon, Derek M, Kellman, Peter, Moon, James C, Hausenloy, Derek J, Garg, P., Hassell, M, Foley, J., Ripley, D.P., Dobson, L., Swoboda, P.P., Fent, G., Musa, T.A., Erhayiem, B., Haaf, P., Greenwood, J.P., Nijveldt, R., Westenberg, J.J.M., Geest, R.J.V.D., Plein, S., Rodrigues, Jonathan C L, Amadu, Antonio Matteo, Dastidar, Amardeep Ghosh, Szantho, Gergley, Lyen, Stephen, Godsave, Cattleya, Ratcliffe, Laura E K, Burchell, Amy E, Hart, Emma C, Hamilton, Mark C K, Nightingale, Angus K, Paton, Julian F R, Manghat, Nathan E, Bucciarelli-Ducci, Chiara, Hafyane, Tarik, Teixeira, Tiago, Greiser, Andreas, Mongeon, Francois Pierre, Haifa, Almutairi, Mohammed, Khanji, Redha, Boubertakh, Marc, Miquel, Steffen, Petersen, Greulich, S., Kitterer, D., Latus, J., Henes, J., Kurmann, R., Gloekler, S., Wahl, A., Buss, S., Katus, H., Bobbo, M., Lombardi, M., Braun, N., Alscher, M.D., Sechtem, U., Mahrholdt, H., Meloni, A., Neri, M.G., Preziosi, P., Grassedonio, E., Schicchi, N., Keilberg, P., Pulini, S., Facchini, E., Positano, V., Pepe, A., Nazir, Sheraz A., Shetye, Abhishek, Khan, Jamal N., Singh, Anvesha, Kanagala, Prathap, Swarbrick, Daniel, Gulsin, Gaurav, Graham-Brown, Matthew, Squire, Iain, Gershlick, Anthony, McCann, Gerry P., Stefan Biesbroek, P., Amier, Raquel P., Teunissen, Paul F.A., Robbers, Lourens F.H.J., Beek, Aernout M., van Rossum, Albert C., Hofman, Mark B.M., van Royen, Niels, Nijveldt, Robin, Arenja, Nisha, Riffel, Johannes H, Djiokou, Charly Noel, Andre, Florian, Fritz, Thomas, Halder, Manuel, Thomas, Zelniker, Korosoglou, Grigorios, Katus, Hugo A, Buss, Sebastian J, Kammerlander, Andreas A., Schwaiger, Marianne L., Duca, Franz, Aschauer, Stefan, Marzluf, Beatrice A., Zotter-Tufaro, Caroline, Dalos, Daniel, Pfaffenberger, Stefan, Bonderman, Diana, Mascherbauer, Julia, Sayeed, Aatif, Fridman, Yaron, Hackman, Brianne, Kadakkal, Ajay, Maanja, Maren, Daya, Hussein Abu, Wong, Timothy C., Schelbert, Erik B., Ricci, F., Barison, A., Todiere, G., Gaeta, R., Galllina, S., Emdin, M., De Caterina, R., Aquaro, G.D., Bernhardt, Peter, Buckert, Dominik, Dyckmanns, Nils, Rottbauer, Wolfgang, Meierhofer, Christian, Kühn, Andreas, Shehu, Nerejda, Müller, Jan, Stern, Heiko, Ewert, Peter, Fratz, Sohrab, Vogt, Manfred, Devos, Daniel G.H., De Groote, Katya, Babin, Danilo, Demulier, Laurent, Taeymans, Yves, Westenberg, Jos J., Van Bortel, Luc, Segers, Patrick, Achten, Eric, De Schepper, Jean, Rietzschel, Ernst, Ruecker, Beate, Geiger, Julia, Makki, Malek, Burkhardt, Barbara, Kellenberger, Christian J., Buechel, Emanuela R. Valsangiacomo, Burkhardt, B.E.U., Kellenberger, C.J., Geiger, J., Ruecker, B., Buechel, E.R. Valsangiacomo, Kamphuis, Vivian P., Elbaz, Mohammed S.M., Kroft, Lucia J.M., van der Geest, Rob J., de Roos, Albert, Blom, Nico A., Westenberg, Jos J.M., Roest, Arno A.W., De Lazzari, Manuel, Cipriani, Alberto, Susana, Angela, Rizzo, Stefania, Giorgi, Benedetta, Carmelo, Lacognata, Bertaglia, Emanuele, Bauce, Barbara, Corrado, Domenico, Thiene, Gaetano, Marra, Martina Perazzolo, Basso, Cristina, Iliceto, Sabino, Nederend, I., Roest, A.A.W., van den Boogaard, P.J., ten Harkel, A.D.J., de Geus, J.C.N., Kroft, L.J.M., de Roos, A., Westenberg, J.J.M., Dux-Santoy, Lydia, Kale, Raquel, Teixido-Tura, Gisela, Maldonado, Giuliana, Huguet, Marina, Garcia-Dorado, David, Evangelista, Artur, Rodriguez-Palomares, Jose, Cavalcante, João L., Rijal, Shasank, Schindler, John T., Gleason, Thomas G., Lee, Joon S., Schelbert, Erik B., Rosmini, Stefania, Bulluck, Heerajnarain, Treibel, Thomas A, Bhuva, Anish, Abdel-Gadir, Amna, Culotta, Veronica, Merghani, Ahmed, Maestrini, Viviana, Herrey, Anna S, Kellman, Peter, Manisty, Charlotte, Moon, James C, Liu, B., Hayer, M.K., Baig, S., Shah, T., Rooney, S.J., Edwards, N.C., Steeds, R.P., Fent, G.J., Garg, P., Swoboda, P., Dobson, L.E., Musa, T.A., Foley, J.F., Haaf, P., Greenwood, J.P., Plein, S., Claessen, G., Schnell, F., Bogaert, J., Dymarkowski, S., Pattyn, N., Claus, P., Van Cleemput, J., Gerche, A. La, Heidbuchel, H., Behar, Jonathan, Toth, Daniel, Reiml, Sabrina, Panayiotou, Maria, Claridge, Simon, Jackson, Tom, Sohal, Manav, Webb, Jessica, O'Neill, Mark, Brost, Alexander, Mountney, Peter, Razavi, Reza, Rhode, Kawal, Rinaldi, Christopher Aldo, Oebel, S., Arya, A., Hilbert, S., Bollmann, A., Hindricks, G., Jahnke, C., Paetsch, I., Dinov, B., Baritussio, A., Perazzolo Marra, M., Ghosh Dastidar, A., Rodrigues, J., Zorzi, A., Susana, A., Scatteia, A., De Garate, E., Mattesi, G., Strange, J., Corrado, D., Bucciarelli-Ducci, C., Ranjit Arnold, J., Jerosch-Herold, Michael, Karamitsos, Theodoros D., Francis, Jane M., Bhamra-Ariza, Paul, Sarwar, Rizwan, Choudhury, Robin, Selvanayagam, Joseph B., Neubauer, Stefan, Tayal, Upasana, Scott, Andrew D, Wage, Rick, Ferreira, Pedro, Pennell, Dudley, Zhong, Xiaodong, Epstein, Fred, Firmin, David, Prasad, Sanjay, Kallifatidis, Alexandros, Prousalis, Anastasios, Mouratoglou, Sophia-Anastasia, Giannakoulas, George, Deligianni, Xenia, Bakaloudis, Michail, Magganaris, Nikolaos, Sianos, George, Karvounis, Haralampos, Santini, Francesco, Garg, P., Aziz, R., Foley, J.R.J., Fent, G., Musa, T.A., Haaf, P., Dobson, L., Swoboda, P.P., Greenwood, J.P., Plein, S., Geest, R.J.V.D., Westenberg, J.J.M., Beitzke, D., Rasul, S., Wadsak, W., Mitterhauser, M., Nolz, R., Stelzmueller, M., Loewe, C., Hacker, M., Funk, Stephanie, Kermer, Josephine, Dogangüzel, Serkan, von Knobelsdorff-Brenkenhoff, Florian, Schulz-Menger, Jeanette, Kolker, Shimon, Weisz, Giora, Bogot, Naama, Halpern, Irit Hadas, Wolak, Arik, Rutz, Tobias, Ginami, Giulia, Piccini, Davide, Coppo, Simone, Vincenti, Gabriella, Stuber, Matthias, Schwitter, Jürg, Safdar, Komal S, Gao, Xuexin, Ambach, Stephanie, Taylor, Michal D, Moore, Ryan, Taylor, Robin J, Toro-Salazar, Olga, Jeffries, John L, Bartone, Cheryl, Raman, Subha V, Mazur, Wojciech, Valente, F., Rodriguez-Palomares, J.F., Gutierrez, L., Pineda, V., Agliano, B., Galian, L., Teixido, G., Gonzalez-Alujas, M.T., Evangelista, A., Garcia-Dorado, D., Murdoch, R., Gandy, S., Nicholas, R., Houston, G., Martin, P., Muir, J., Matthew, S., Ramkumar, P. Guntur-, Cavin, I., Macaione, F., Barison, A., Pescetelli, I., Pali, F., Pizzino, F., Terrizzi, A., Di Lisi, D., Novo, G., Todiere, G., Assennato, P., Novo, S., Aquaro, G.D., Dastidar, Amardeep Ghosh, McAlindon, Elisa, Rodrigues, Jonathan, Baritussio, Anna, Scatteia, Alessandra, De Garate, Estefania, Benny Lawton, Chris, Erdei, Tamas, Szantho, Gergely, Hamilton, Mark, Bucciarelli-Ducci, Chiara, Pontone, Gianluca, Andreini, Daniele, Rota, Cristina, Guglielmo, Marco, Mushtaq, Saima, Baggiano, Andrea, Beltrama, Virginia, Solbiati, Anna, Guaricci, Andrea I., Pepi, Mauro, Grigoratos, Chrysanthos, Bratis, Konstantinos, Henningson, Markus, Dell'Omodarme, Matteo, Puntmann, Valentina O., Nagel, Eike, Meloni, Antonella, Giunta, Nicola, Giuliano, Pietro, Neri, Maria Giovanna, Restaino, Gennaro, Renne, Stefania, Quota, Alessandra, Positano, Vincenzo, De Marchi, Daniele, Pepe, Alessia, Pedrotti, Patrizia, Campadello, Paola, Masciocco, Gabriella, Facchetti, Rita, Milazzo, Angela, Quattrocchi, Giuseppina, Giannattasio, Cristina, Frigerio, Maria, Roghi, Alberto, Rimoldi, Ornella, De Garate, Estefania, Ghosh Dastidar, Amardeep, Baritussio, Anna, Scatteia, Alessandra, Amadu, Antonio, Venuti, Giuseppe, Rodrigues, Jonathan C., Bucciarelli-Ducci, Chiara, Careri, Giulia, Castelvecchio, Serenella, Camporeale, Antonia, Secchi, Francesco, Menicanti, Lorenzo, Lombardi, Massimo, Kockova, R., Sedlacek, K., Wichterle, D., Sikula, V., Tintera, J., Sukupova, L., Kautznerova, D., Segetova, M., Praveckova, A., Langova, R., Kryze, L., El-Husseini, W., Kautzner, J., Oebel, S., Dinov, B., Arya, A., Hilbert, S., Sommer, P., Bollmann, A., Hindricks, G., Paetsch, I., Jahnke, C., Nazir, Sheraz A., Greenwood, John P., Shetye, Abhishek, Khan, Jamal N., Singh, Anvesha, Kanagala, Prathap, Swarbrick, Daniel, Gulsin, Gaurav, Graham-Brown, Matthew, Gershlick, Anthony, McCann, Gerry P., Grigoratos, Chrysanthos, Liga, Riccardo, Bennatti, Elena, Barison, Andrea, Todiere, Giancarlo, Aquaro, Giovanni Donato, Dell'Omodarme, Matteo, Lombardi, Massimo, Emdin, Michele, Masci, Pier Giorgio, Barison, A, Ortalda, A, Todiere, G, Grigoratos, C, Vergaro, G, Mirizzi, G, Martini, N, De Marchi, D, Keilberg, P, Passino, C, Aquaro, GD, Emdin, M, Swoboda, Peter P, McDiarmid, Adam K, Erhayiem, Bara, Fent, Graham J, Dobson, Laura E, Garg, Pankaj, Musa, Tarique A, Foley, James R, Page, Stephen P, Greenwood, John P, Plein, Sven, Bulluck, Heerajnarain, Rosmini, Stefania, Abdel-Gadir, Amna, Bhuva, Anish, Treibel, Thomas A, White, Steven K, Fontana, Marianna, Ramlall, Manish, Hamarneh, Ashraf, Sirker, Alex, Herrey, Anna, Manisty, Charlotte, Yellon, Derek M, Kellman, Peter, Moon, James C, Hausenloy, Derek J, Broncano, J., Luna, A., Noguerol, T. Martin –, Caro, P., Toro-Cebada, R., Gonzalez, J. Sanchez –, Desroche, L.M., Milleron, O., Safar, B., Lavie-Badie, Y., Millischer, D., Abtan, J., Jondeau, G., Bermejo, Zorba Blázquez, Cuesta, Emilio, Rosillo, Sandra O., Guzmán, Gabriela, Pinilla, Inmaculada, González, Óscar, Caro, Juan, Ponz, Inés, López, Teresa, Refoyo, Elena, Kozor, Rebecca, Nordin, Sabrina, Treibel, Thomas A, Rosmini, Stefania, Castelleti, Silvia, Fontana, Marianna, Captur, Gabriella, Steeds, Rick, Baig, Shanat, Manisty, Charlotte, Grieve, Stuart M, Figtree, Gemma A, Moon, James C, Dastidar, Amardeep Ghosh, Rodrigues, Jonathan, De Garate, Estefania, Singhal, Priyanka, McAlindon, Elisa, Baritussio, Anna, Scatteia, Alessandra, Erdei, Tamas, Strange, Julian, Nightingale, Angus, Baumbach, Andreas, Johnson, Tom, Delgado, Victoria, Bucciarelli-Ducci, Chiara, Lapinskas, Tomas, Bucius, Paulius, Fedaravicius, Augustinas P., Urbonaite, Laura, Stabinskaite, Agnieta, Zaliunas, Remigijus, Elisabetta, Chiodi, Teresa, Cannizzaro Maria, Daniele, De Falco Alfano, Righi, Riccardo, Zerbini, Michela, Vincenzo, Positano, Cittanti, Corrado, Giganti, Melchiore, Giorgio, Benea, Grigoratos, Chrysanthos, Genovesi, Dario, Giorgetti, Assuero, Chiappino, Sara, Barison, Andrea, Vergaro, Giuseppe, Todiere, Giancarlo, Emdin, Michele, Marzullo, Paolo, Aquaro, Giovanni Donato, Ladeiras-Lopes, Ricardo, Turin-Moreira, Henrique, Bettencourt, Nuno, Fontes-Carvalho, Ricardo, Sampaio, Francisco, Ambale-Venkatesh, Bharath, Wu, Colin, Liu, Kiang, Bertoni, Alain, Ouyang, Pamela, Bluemke, David, Lima, João, Fent, GJ., Garg, P., Dobson, LE., Musa, TA., Foley, JF., Haaf, P., Greenwood, JP., Plein, S., Swoboda, PP., Abdul Rahman, E., Ismail, JR., Najme Khir, R., Lim, CW., Chua, N., Ibrahim, ZO., Zainal Abidin, HA., Mohd Arshad, MK., Kasim, SS., Rodrigues, Jonathan, Rooms, Ben, Hyde, Katie, Rohan, Stephen, Dastidar, Amardeep Ghosh, Hamilton, Mark, Bucciarelli-Ducci, Chiara, Nightingale, Angus, Paton, Julian, Manghat, Nathan, MacIver, David, Gibelli, Giuseppe, Demolli, Walter, Russo, Alessandra, Minoia, Chiara, Biasi, Salvatore, Mkrtchyan, Naira, Eltschkner, Christin, Christian, Meierhofer, Ewert, Peter, Martinoff, Stefan, Stern, Heiko, Fratz, Sohrab, Valinoti, Maddalena, Fabbri, Claudio, Mantovan, Roberto, Severi, Stefano, Corsi, Cristiana, Nyktari, E., Vassiliou, V., Arzanauskaite, M., Izgi, C., Lam, W., Prasad, S., Reindl, Martin, Reinstadler, Sebastian Johannes, Feistritzer, Hans-Josef, Klug, Gert, Mair, Johannes, Mayr, Agnes, Jaschke, Werner, Franz, Wolfgang-Michael, Metzler, Bernhard, Arnhold, K., Muehlberg, F., Fritschi, S., Funk, S., Prothmann, M., von Knobelsdorff-Brenkenhoff, F., Schulz-Menger, J., Lakhani, Zeeshan S. A., Mohan, B., karthik, G A., Raj, Vimal, Weir-McCall, Jonathan, Cassidy, Deirdre B, Belch, Jill JF, Gandy, Stephen J, Houston, Graeme, Lambert, Matthew A, Littleford, Roberta, Rowland, Janice, Struthers, Allan D, Khan, Faisel, Camaioni, Claudia, Salel, Marjorie, Hennig, Alexia, Corneloup, Olivier, Montaudon, Michel, Laurent, Francois, Cochet, Hubert, Kan, Rachel, Erhayiem, Bara, McDiarmid, Adam K., Garg, Pankaj, Dobson, Laura E., Musa, Tarique A., Ripley, David, Ajjan, Ramzi, Greenwood, John P., Plein, Sven, Swoboda, Peter P., Reinstadler, Sebastian J., Fuernau, Georg, Eitel, Charlotte, de Waha, Suzanne, Desch, Steffen, Metzler, Bernhard, Schuler, Gerhard, Thiele, Holger, Eitel, Ingo, Feistritzer, Hans-Josef, Reinstadler, Sebastian Johannes, Klug, Gert, Reindl, Martin, Mair, Johannes, Mayr, Agnes, Franz, Wolfgang-Michael, Metzler, Bernhard, Feistritzer, Hans-Josef, Klug, Gert, Reinstadler, Sebastian Johannes, Reindl, Martin, Mayr, Agnes, Franz, Wolfgang-Michael, Metzler, Bernhard, Festa, P., Cadoni, A., D'andrea, C., Costa, S., Keilberg, P., Lunardini, A., Ali, L. Ait, Ali, L. Ait, Aquaro, GD., Peritore, G., Ricci, F., De Marchi, D., Passino, C., Festa, P., Martínez, A. Tercero, Cuartero, J. Navarro, Soriano, J.G. Córdoba, Núñez, S. Calero, de Galarreta, T. Cros Ruiz, García, M. Villar, Page, J.C. Gallego, López, J.C. García, Ruiz, M. Barambio, Erdei, Tamas, Rodrigues, Jonathan C., McIntyre, Bethannie, Dastidar, Amardeep Ghosh, Burchell, Amy E., Ratcliffe, Laura, Hart, Emma C., Paton, Julian F., Hamilton, Mark, Nightingale, Angus K., Manghat, Nathan E., Orii, Makoto, Tanimoto, Takashi, Ota, Shingo, Nishiguchi, Tsuyoshi, Tsujioka, Hiroto, Kuroi, Akio, Yamano, Takashi, Matsuo, Yoshiki, Ino, Yasushi, Kitabata, Hironori, Kubo, Takashi, Tanaka, Atsushi, Hozumi, Takeshi, Akasaka, Takashi, Sousa, Alexandra, Pinho, Teresa, Canedo, Paulo, Lopes, Luís, Azevedo, Olga, Madureira, António, Belo, Adriana, Cardoso, José Silva, Machado, José Carlos, Martins, Elisabete, Brzozowska-Czarnek, Agata, Urbanik, Andrzej, Brzozowska-Czarnek, Agata, Urbanik, Andrzej, Rakowski, Tomasz, Agudo-Quílez, P., Pozo-Osinalde, E., Viliani, D., Olivera, MJ., Caballero, P., Jiménez-Borreguero, LJ., Alfonso, F., Carrabba, Nazario, Angeloni, Giulia, Migliorini, Angela, Valenti, Renato, Parodi, Guido, Antoniucci, David, Almeida-Morais, Luís, Galrinho, Ana, Moura-Branco, Luísa, Tavares-Jalles, Nuno, António, Marta, Abreu, João, Timóteo, Ana Teresa, Pinto-Teixeira, Pedro, Aguiar-Rosa, Sílvia, Rodrigues, Inês, Modas-Daniel, Pedro, Cruz-Ferreira, Rui, Bica, R., Dobre, D., Stanciu, S., Acatrinei, E., Nour, A., Stefan, L., Calistru, P., Rajewska-Tabor, J., Pyda, M., Janus, M., Siniawski, A., Rajewska-Tabor, J., Pyda, M., Janus, M., Siniawski, A., Shaheen, Sameh Mohamed, Elhammady, Walid Abdel-Azim, Ahmed, Mohamed Ismail, Abdel-Hakim, Ahmed Samir, Allam, Lamyaa Elsayed, Helal, Ayman Mohamed, Inage, Akio, Mizuno, Naokazu, Inage, Akio, Mizuno, Naokazu, TEIS, Albert, JUNCÀ, Gladys, ARCE, Javier, ARMARIO, David, Cescau, Arthur, Logeart, Damien, Gelen, Barnabas, Derumeaux, Genevie`ve, Vicaut, Eric, Mercadier, Jean-Jacques, Sirol, Marc, Cipriani, Alberto, De Lazzari, Manuel, Susana, Angela, Zorzi, Alessandro, Baritussio, Anna, Siciliano, Mariachiara, Marinato, Martina, Prevedello, Francesca, Giorgi, Benedetta, Vezzaro, Roberto, Corrado, Domenico, Marra, Martina Perazzolo, von Roeder, M., Rommel, K.-P., Kowallick, J.T., Blazek, S., Fengler, K., Lotz, J., Hasenfuß, G., Lücke, Ch., Gutberlet, M., Schuler, G., Schuster, A., Lurz, Ph., Mahmoud, Ahmad A., Rifaie, Osama, Samir, Ahmed, Allam, Lamyaa, Duca, Franz, Kammerlander, Andreas A., Zotter-Tufaro, Caroline, Aschauer, Stefan, Bonderman, Diana, Mascherbauer, Julia, She, Hoi Lam, Roest, Arno A.W., van den Boogaard, Pieter J., Calkoen, Emmeline E., van der Geest, Rob J., Hazekamp, Mark G., de Roos, Albert, Westenberg, Jos J.M., Burkhardt, B.E.U., Kellenberger, C.J., Geiger, J., Ruecker, B., Buechel, E.R. Valsangiacomo, Bainbridge, G., Garg, P., Foley, J.R.J., Fent, G., Musa, T.A., Haaf, P., Dobson, L., Swoboda, P.P., Greenwood, J.P., Plein, S., Charalambos, Max, Rodrigues, Jonathan, Burchell, Amy, Dastidar, Amardeep Ghosh, BSc(Hons), Laura Ratcliffe, Hart, Emma, Hamilton, Mark, Paton, Julian, Nightingale, Angus, Manghat, Nathan, Muñoz, Begoña Igual, Monserrat, Adrian, gonzalez, Alicia Maceira, Tuset, Luis, Miro, Vicente, Hernandiz, Amparo, Fernandez, Rubén, Sauri, Asunción, Sepúlveda, Pilar, Diez, Jose Luis, Montero, Anastasio, Contaldi, Carla, Imbriaco, Massimo, Alcidi, Gianmarco, Ponsiglione, Andrea, Santoro, Ciro, Puglia, Marta, Barbuto, Luigi, Cuocolo, Alberto, Trimarco, Bruno, Galderisi, Maurizio, Muñoz, Begoña Igual, Sanchez, Elena, Plaza, Diego, sanchis, Pilar Sepúlveda, Gonzalez, Alicia Maceira, Hernandiz, Amparo, Miro, Vicente, vazquez, Alex, Diez, Jose Luis, Martinez, Luis, Montero, Anastasio, Muñoz, B. Igual, Alfredo, Hernandez Caballero, Diana, Domingo Valero, Alicia, Maceira Gonzalez, Jordi, Estornell Erill, Jose, Valera martinez Francisco, Alejandro, Vazquez Sanchez, Anastasio, Montero Argudo, Mochula, O.V., Shelkovnikova, T.A., Popov, S.V., Lukyanenok, P.I., Shelupanov, A.A., Oferkin, A.I., Bakhmet'eva, T.A., Ussov, W.Yu., van den Bosch, Harrie CM., Westenberg, Jos JM., Setz-Pels, Wikke, Kersten, Erik, Tielbeek, Alexander, Duijm, Lucien EM., Post, Johannes, Teijink, Joep A.W., de Roos, Albert, Frick, M., Kirschfink, A., Mühler, E., Marx, N., Hövels-Gürich, H., Gert, Klug, Hans-Josef, Feistritzer, Sebastian, Reinstadler, Martin, Reindl, Benjamin, Seidner, Agnes, Mayr, Sylvana, Müller, Bernhard, Metzler, Fawal, aSara E., Zidan, aMamdouh, Webb, Jessica, Holub, Ondrej, Clough, Rachel, Carr-White, Gerald, Razavi, Reza, Sinkus, Ralph, Maksimova, A.S., Bobrikova, E.E., Bukhovets, I.L., Plotnikov, M.P., Rogovskaya, Yu.V., Rebenkova, M.S., Usov, W.Yu., Mayr, Agnes, Klug, Gert, Feistritzer, Hans-Josef, Reinstadler, Sebastian Johannes, Reindl, Martin, Metzler, Bernhard, Kremser, Christian, Schocke, Michael, Winter, M.M., Pluchinotta, F.R., Giusti, G., Secchi, F., Piazza, L., Carminati, M., Chessa, M., Bokma, J.P., Bouma, B.J., Mulder, B.J., Lombardi, M., Katia, Menacho, Thomas, Treibel, Rebecca, Kozor, Heeraj, Bulluck, James, Moon, Charlotte, Manisty, Sztajzel, Juan, Bertron, Fabienne, Papavassiliu, Theano, Oezkan, Sueheyla, Lossnitzer, Dirk, Schoenberg, Stefan O., Borggrefe, Martin, Doesch, Christina, Baig, S., Edwards, NC., Liu, B., Hayer, MK., Dawson, CH., Geberhiwot, T., Steeds, RP., Shehu, N., Stern, H., Mkrtchyan, N., Meierhofer, C., Martinoff, S., Ewert, P., Fratz, S., Pais, João, Picarra, Bruno, Santos, Ana Rita, Guerreiro, Rui, Congo, Kisa Hyde, Carvalho, João, Neves, David, Aguiar, José, Vinco, Giulia, Fischer, Kady, Labelle, Chantal, Gelineau, Sylvie, Farkas, Sandra, Lebel, Julie, Friedrich, Matthias G., Webb, Jessica, Villa, Adriana, Bekri, Imane, Shome, Joy, Teall, Tom, Di Giovine, Gabriella, Sammut, Eva, Carr-White, Gerald, Al-Fakih, Khaled, Chiribiri, Amedeo, Kamphuis, Vivian P., Roest, Arno AW., Kroft, Lucia JM., van der Geest, Rob J., de Roos, Albert, Blom, Nico A., Westenberg, Jos JM., Elbaz, Mohammed SM., Bensaoud, M., Soufiani, A., Barahioui, H., Bayi, A., Fellat, N., Benjelloun, H., Tazi, Z., Abawi, Masieh, Elisabetta, Chiodi, Teresa, Cannizzaro Maria, Daniele, De Falco Alfano, Righi, Riccardo, Zerbini, Michela, Vincenzo, Positano, Cittanti, Corrado, Giganti, Melchiore, Giorgio, Benea, Elisabetta, Chiodi, Teresa, Cannizzaro Maria, Daniele, De Falco Alfano, Righi, Riccardo, Zerbini, Michela, Vincenzo, Positano, Cittanti, Corrado, Giganti, Melchiore, Giorgio, Benea, Musa, TA., Uddin, A., Dobson, LE., Swoboa, PP., Garg, P., Fent, GJ., Foley, JRJ., Malkin, CJ., Plein, S., Blackman, DJ., Greenwood, JP., Yun, Chun-Ho, Bezerra, Hiram G., Richmond, C., Dobson, LE., Swoboda, PP., Musa, TA., Foley, JF., Garg, P., Haaf, P., Fent, GJ., Plein, S., Greenwood, JP., Meloni, Antonella, Gamberini, Maria Rita, Neri, Maria Giovanna, Cuccia, Liana, D'Ascola, Domenico Giuseppe, Tudisca, Chiara, Vinci, Valentina, Positano, Vincenzo, Pepe, Alessia, Meloni, Antonella, Borgna-Pignatti, Caterina, Del Vecchio, Giovanni Carlo, Romeo, Maria Antonietta, Gamberini, Maria Rita, Bonetti, Federico, Neri, Maria Giovanna, Missere, Massimiliano, Salvatori, Cristina, Pepe, Alessia, Dobson, LE., Musa, TA., Uddin, A., Fairbairn, TA., Bebb, OJ., Swoboda, PP., Haaf, P., Foley, J., Garg, P., Fent, GJ., Malkin, CJ., Blackman, DJ., Plein, S., Greenwood, JP., Schneeweis, C., Eckert, J., Tröbs, M., Magedanz, A., Schmidt, M., Voigtländer, T., Schmermund, A., Achenbach, S., Foley, JRJ., Dobson, LE., Musa, TA., Swoboda, PP., Garg, P., Fent, GF., Haaf, P., Malkin, CJ., Blackman, DJ., Plein, S., Greenwood, JP., Matthew, S., McCall, J. Weir, Gandy, S.J., Milne, W.G., Houston, J.G, Meloni, A., Ricchi, P., Spasiano, A., Neri, MG., Vallone, A., Resta, MC., Righi, R., Keilberg, P., Santamaria, V., Positano, V., Pepe, A., Henein, Michael Y., Bengrid, Tarek, Nicoll, Rachel, Zhao, Ying, Johansson, Bengt, Schmermund, Axel, Barbanti, Marco, Cascone, Irene, Miccichè, Eligio, Buccheri, Sergio, Immè, Sebastiano, Pilato, Gerlando, Tamburino, Claudia, Patanè, Martina, Gulino, Simona, Todaro, Denise, Salerno, Tatiana, Garretto, Valeria, Privitera, Gianbattista, Capodanno, Davide, Tamburino, Corrado, Manna, Alessio La, Vincenti, Gabriella, Masci, Pier-Giorgio, Rutz, Tobias, De Blois, Jonathan, Schwitter, Juerg, Monney, Pierre, Paelinck, Bernard P., Vandendriessche, Tom, De Bock, Dina, Parizel, Paul M., Rodrigus, Inez E., Claeys, Marc J., Leone, D., Tosello, F., Bruno, G., Avenatti, E., Faletti, R., Ravera, A, Veglio, F., Milan, A., Meloni, A., Maggio, A., Leto, F., Pitrolo, L., De Marchi, D., Positano, V., Neri, MG., Pepe, A., Pizzino, F., Meloni, A., Terrizzi, A., Aquaro, GD., Neri, MG., Spasiano, A., Serra, M., Allò, M., Keilberg, P., Positano, V., Di Bella, G., Zito, C., Pepe, A., Saunders, Laura, Stewart, Neil J., Hammerton, Charlotte, Capener, David, Puntmann, Valentina O, Graves, Martin J., Kiely, David G., Wild, Jim M., Swift, Andrew J., Macaione, F., Meloni, A., Barison, A., Neri, MG., Positano, V., Salvatore, N., Assennato, P., Pepe, A., Kammerlander, Andreas A., Aschauer, Stefan, Marzluf, Beatrice A., Zotter-Tufaro, Caroline, Duca, Franz, Knechtelsdorfer, Klaus, Wiesinger, Matthias, Dalos, Daniel, Pfaffenberger, Stefan, Bonderman, Diana, Mascherbauer, Julia, Haberka, Maciej, Sosnowski, Maciej, Gasior, Zbigniew, Aslam, Sajid, El-Hamamsy, Ismail, SM, Francois-Pierre Mongeon, Bethke, Anne, Eritsland, Jan, Shanmuganathan, Limalanathan, Abdelnoor, Mikael, Andersen, Geir Øystein, Kløw, Nils Einar, Hoffmann, Pavel, Bouhzam, Najime, Caudron, Jérôme, Tron, Christophe, Camacho, Carlos Rodriguez, Cribier, Alain, Dacher, Jean Nicolas, Eltchaninoff, Hélène, Foley, JRJ., Garg, P., Musa, TA., Dobson, LE., Swoboda, PP., Fent, GJ., Haaf, P., Plein, S., Greenwood, JP., Heck, Siri Lagethon, Gulati, Geeta, Von Knobelsdorff-Brenkenhoff, Florian, Storas, Tryggve Holck, Schulz-Menger, Jeanette, Hoffmann, Pavel, Omland, Torbjørn, Kermer, J., Traber, J., Utz, W., Hennig, P., Menza, M., Jung, B., Greiser, A., Kuijer, J., Barckow, P., von Knobelsdorff-Brenkenhoff, F., Töpper, A., Schulz-Menger, J, Malanchini, Giovanni, Moscatelli, Sara, Di Giovine, Gabriella, Balzarini, Luca, Del Corral, Maria Pia, Gasparini, Gabriele, Montini, Orsola, Monti, Lorenzo, Aquaro, Giovanni Donato, Briatico, Alessandra, Toia, Patrizia, Barison, Andrea, Ait-Ali, Lamia, Midiri, Massimo, Cotroneo, Antonio Raffaele, Festa, Pierluigi, Aquaro, G.D., Pizzino, F., Terrizzi, A., Todiere, G., Grigoratos, C., Barison, A., Di Bella, G., Igual-Muñoz, Begoña, de Carranza, María Jose Sancho-Tello, Maceira-Gonzalez, Alicia, Buendía-Fuentes, Francisco, Estornell-Erill, Jordi, Cano-Perez, Oscar, Montero, Anastasio, Igual, Begoña, Sanz, Jorge, Maceira, Alicia, Miro, Vicente, Minguez, Ana Bel, Guillen, Manuel Perez, Lopez, Raquel, Vazquez, Alex, Diez, Jose Luis, rené, Oscar, sepúlveda, Pilar, argudo, Anastasio Montero, Roy, Clotilde, Slimani, Alisson, Amzulescu, Mihaela, de Ravenstein, Christophe de Meester, Pasquet, Agnès, Vancraeyenest, David, Vanoverschelde, Jean-Louis, Gerber, Bernhard, Pouleur, Anne-Catherine, Scatteia, Alessandra, Rodrigues, Jonathan, Lyen, Stephen, De Gerate, Estefania, Baritussio, Anna, Dastidar, Amardeep Ghosh, Maceira, Alicia, Pennell, Dudley, Bucciarelli-Ducci, Chiara, Katulska, Katarzyna, Kociemba, Anna, Rajewska-Tabor, Justyna, Janus, Magdalena, Siniawski, Andrzej, Stajgis, Marek, Pyda, Małgorzata, Brzostowicz, Tomasz, Brzostowicz, Marta, Gibbs, TGJ, Villa, AD, Sammut, E, Mullen, G, Ganeshan, B, Chiribir, A, Singh, Anvesha, McCann, Gerry P, Investigators, the PRIMID-AS, Le, Thu-Thao, Su, Boyang, Cai, Jiasheng, Han, Yiying, Tan, Ru San, Cook, Stuart A, Chin, Calvin WL, Scatteia, Alessandra, Vollema, E. Mara, Leung, Melissa, Marsan, Nina Ajmone, Baritussio, Anna, De Garate, Estefania, Dastidar, Amardeep Ghosh, Rodrigues, Jonathan, Bax, Jeroen J, Delgado, Victoria, Bucciarelli-Ducci, Chiara, Baritussio, A., De Garate, E., Dastidar, A. Ghosh, Ahmed, N., Scatteia, A., Rodrigues, J., Lawton, C., Thomas, Glyn, Duncan, Edward, Cripps, Tim, Diab, Ihab, Bucciarelli-Ducci, C., Treibel, TA., Fontana, M., Kozor, R., Macrae, R., Malcolmson, JW., Menacho, KD., Scully, PR., Lawrence, DR., Sheikh, AM., Herrey, AS., Manisty, C., Moon, JC., Hinojar, R., Golfin, C. Fernandez, Portugal, JC., Esteban, A., Megias, A., Gomez, A. Gonzalez, Rincon, LM., Nacher, JJ. Jimenez, Zamorano, JL., Valente, F., Gutierrez, L., Maldonado, G., Pineda, V., Agliano, B., Galian, L., Teixido, G., Gonzalez-Allujas, MT., Evangelista, A., Garcia-Dorado, D., Rodriguez-Palomares, JF., Fratz, Sohrab, Belker, Kristina, Naumann, Susanne, Martinoff, Stefan, Stern, Heiko, Shehu, Nerejda, Mkrtchyan, Naira, Meierhofer, Christian, Eicken, Andreas, Ewert, Peter, Hilbert, Sebastian, Weber, Alexander, Oebel, Sabrina, Hindricks, Gerhard, Jahnke, Cosima, Paetsch, Ingo, van der Palen, RLF., Roest, AAW., van den Boogaard, PJ., Blom, NA., de Roos, A., Westenberg, JJM., Piatti, Filippo, Sturla, Francesco, Pirola, Selene, Votta, Emiliano, Nesteruk, Igor, Lombardi, Massimo, Corte, Alessandro Della, Bissell, Malenka, Caiani, Enrico Gianluca, Redaelli, Alberto, Berlot, B., Golfin, C. Fernandez, Hinojar, R., Esteban, A., Mendez, MA Fernandez, Megias, A., Gomez, A. Gonzalez, García, A., Alonso, G., Marco, A., Casas, E., Nacher, JJ. Jimenez, Zamorano, JL., Baggi, Chiara, Piatti, Filippo, Sturla, Francesco, Votta, Emiliano, Pluchinotta, Francesca, Lombardi, Massimo, Redaelli, Alberto, Hinojar, R., Golfin, C. Fernandez, Esteban, A., Mendez, MA Fernandez, Megias, A., Gonzalez Gomez, A., García, A., Alonso, G., Marco, A., Nacher, JJ. Jimenez, Zamorano, JL., McAlindon, Elisa, Dastidar, Amardeep, Bucciarelli-Ducci, Chiara, McAlindon, Elisa, Littlejohns, Ben, Suleiman, Saadeh, Baumbach, Andreas, Bucciarelli-Ducci, Chiara, McAlindon, Elisa, Vizzi, Vincenzo, Baumbach, Andreas, Bucciarelli-Ducci, Chiara, Tanaka, Kaoru, Fierens, Yves, Nijs, Jan, De Mey, Johan, Lai, Peng, Raeymaekers, Hubert, Elbaz, Mohammed S.M., Toger, Johannes, Heiberg, Einar, Westenberg, Jos J., Solana, Ana Beatriz, Hafalir, Fatih, Ghedin, Piero, Lai, Peng, Shimakawa, A., Anja, C., Fratz, Sohrab, McGill, Laura-Ann, Ferreira, Pedro, Scott, Andrew D, Nielles-Vallespin, Sonia, Giannakidis, Archontis, J Kilner, Philip, Gatehouse, Peter D, de Silva, Ranil, Firmin, David N, Pennell, Dudley J, Merten, Constanze, Beurich, Hans-Wilko, Zachow, Dirk, El-Mawardy, Mohamed, Abdel-Wahab, Mohamed, Richardt, Gert, Merten, Constanze, Beurich, Hans-Wilko, Zachow, Dirk, Abdel-Wahab, Mohamed, El-Mawardy, Mohamed, Tölg, Ralph, Richardt, Gert, De Garate, Estefania, Biglino, Giovanni, Aileen, Wilson, Dodd, James, Bucciarelli-Ducci, Chiara, Salinas, GL. Alonso, Gómez, A. González, Hinojar, R., Golfín, C. Fernández, Esteban, A., del Castillo, A. Marco, Monteagudo, J., Izco, M. Pascual, Megías, A., Martín, A. García, Nacher, JJ. Jiménez, Zamorano, JL, Dastidar, Amardeep Ghosh, Carpenter, Alexander, Rodrigues, Jonathan, Palazzuoli, Alberto, Wilson, Catherine, Kestenbaum, Samantha, Baritussio, Anna, Baumbach, Andreas, Nightingale, Angus, Bucciarelli-Ducci, Chiara, Dastidar, Amardeep Ghosh, Rodrigues, Jonathan, Szantho, Gergely, McAlindon, Elisa, Baritussio, Anna, Scatteia, Alessandra, De Garate, Estefania, Lawton, Chris Benny, Erdei, Tamas, Manghat, Nathan, Hamilton, Mark, Bucciarelli-Ducci, Chiara, Nazir, Sheraz A., Greenwood, John P., Shetye, Abhishek, Khan, Jamal N., Singh, Anvesha, Kanagala, Prathap, Swarbrick, Daniel, Gulsin, Gaurav, Graham-Brown, Matthew, Gershlick, Anthony, McCann, Gerry P., Pais, João, Picarra, Bruno, Santos, Ana Rita, Guerreiro, Rui, Congo, Kisa Hyde, Carvalho, João, Neves, David, and Aguiar, José

Abstract

Objectives: Myocardial fibrosis in noninfarcted myocardium is emerging as a principal phenotype of vulnerability to adverse events such as mortality and hospitalization for heart failure (HHF), but its optimal noninvasive measurement remains uncertain despite consistently robust histologic validation data for extracellular volume fraction (ECV). We therefore compared ECV, native T1, post contrast T1, the gadolinium contrast partition coefficient (lambda), and the presence of nonischemic scar in their associations with mortality and HHF outcomes. Method: To quantify of myocardial fibrosis, we performed T1 mapping (MOLLI) in basal and mid short axis slices with cardiovascular magnetic resonance (CMR) before contrast and 12-30 minutes post contrast bolus in 1185 consecutive patients without amyloidosis, hypertrophic or stress cardiomyopathy. We assessed associations with outcomes using Kaplan-Meier plots and chi square values from univariable Cox regression models. All standard T1 mapping parameters were obtained: native and post contrast myocardial T1, the partition coefficient lambda, and ECV. ECV = (1-hematocrit) · [ΔR1myocardium]/[ΔR1bloodpool], where R1 = 1/T1 Late gadolinium enhancement imaging with phase sensitive reconstruction identified nonischemic scar. Results: Over a median of 1.7 years, 111 individuals experienced events after CMR: 55 HHF events and 74 deaths. ECV yielded better separation of Kaplan-Meier curves in a dose dependent fashion (Figure) and also stronger associations with the combined endpoint of death or HHF. The ECV chi square (77.3, p < 0.001) was at least twice as large as the Native T1 chi square (37.5, p < 0.001), the lambda chi square (34.8, p < 0.001) and nonischemic scar (chi square = 20.5, p<0.001). Post-contrast T1 was not associated with outcomes, even when adjusting further for time after contrast bolus, renal function, and patient weight (chi square <3, p >0.10). Conclusion: Analogous to histologic previously published validation data, quantitative ECV myocardial fibrosis measures associated with outcomes far stronger than other surrogate measures outcome measures such as native T1, post contrast T1 and nonischemic scar on LGE images. These data suggest that ECV is the noninvasive metric of choice to measure myocardial fibrosis. Figure. Kaplan-Meier Plots for T1 mapping parameters.

Published
2016
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109. Estudo da função ventricular por strain obtido por speckle tracking em doentes com cardiomiopatia hipertrófica

Author

Lourenço, Mário Rui Antunes and Azevedo, Olga

Subjects
cardiovascular system, Miocardiopatia hipertrófica, cardiovascular diseases, Twist, Hypertrophic cardiomyopathy, Speckle tracking, Strain
Abstract

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular - Área de especialização: Ultrassonografia cardiovascular Introdução: A Miocardiopatia Hipertrófica (MCH) é uma miocardiopatia caracterizada pela presença de hipertrofia ventricular esquerda (HVE) e disfunção diastólica. Disfunção sistólica subclínica também ocorre apesar da fracção de ejecção se manter frequentemente conservada até uma fase tardia da doença. A avaliação ecocardiográfica da deformação miocárdica permite detectar e compreender melhor a disfunção sistólica subclínica que ocorre na MCH. Objectivo: Avaliação da função ventricular de doentes com MCH através de strain obtido por speckle tracking, com maior ênfase no twist ventricular. Metodologia: Estudo prospectivo incluindo 20 doentes com MCH, 16 doentes com HVE secundária à hipertensão arterial e 17 controlos. Colhidos dados demográficos e clínicos. Efectuado ecocardiograma transtorácico com avaliação da deformação miocárdica por speckle tracking 2D, incluindo o twist ventricular. Resultados: Os valores globais de strain e strain rate longitudinais foram menores na MCH que nos outros grupos de indivíduos. O twist ventricular estava aumentado nos doentes com MCH comparativamente aos controlos. Mais especificamente, o twist estava aumentado nos doentes com MCH obstrutiva, em comparação com os doentes com MCH não obstrutiva e os controlos, nos quais o twist estava preservado (27.9±9.0º vs. 15.3±4.4º vs. 15.9±5.8º; p=0.001; p=0.001). O aumento do twist nos doentes com MCH obstrutiva deveu-se a um aumento da rotação quer basal quer apical do VE. O gradiente de pressão na câmara de saída do VE foi preditor independente do twist nos doentes com MCH. Conclusões: O twist ventricular está aumentado nos doentes com MCH obstrutiva por aumento da rotação quer basal quer apical do VE. ABSTRACT - Introduction: Hypertrophic cardiomyopathy (HCM) is a cardiomyopathy characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction. Subclinical systolic dysfunction also develops in spite of preservation of left ventricular ejection fraction until a late stage of the disease. Echocardiographic evaluation of strain allows the detection and better understanding of the subclinical systolic dysfunction that occurs in HCM. Aim: Evaluation of left ventricular function in patients with HCM using strain obtained by speckle tracking, particularly ventricular twist. Methods: Prospective study including 20 patients with HCM, 16 patients with LVH secondary to arterial hypertension and 17 healthy controls. Demographic and clinical data were obtained. Transthoracic echocardiogram was performed with evaluation of strain by 2D speckle tracking, including ventricular twist. Results: Global longitudinal strain and strain rate were lower in HCM than in the other groups of individuals. LV twist was increased in patients with HCM, when compared to controls. More specifically, LV twist was increased in patients with obstructive HCM, when compared to patients with nonobstructive HCM and controls, in whom LV twist was preserved (27.9±9.0º vs. 15.3±4.4º vs. 15.9±5.8º; p=0.001; p=0.001). The increase of LV twist in patients with obstructive HCM was due to an increase of basal and apical LV rotation. The pressure gradient on the outflow tract was an independent predictor of LV twist in patients with HCM. Conclusion: LV twist is increased in patients with obstructive HCM due to an increase of basal and apical LV rotation. N/A

Published
2013

110. "Hot phase" clinical presentation of biventricular arrhythmogenic cardiomyopathy: when the perfect electrical storm spontaneously stops.

Author

Gomes Tinoco M, Castro M, Pinheiro L, Pereira T, Oliveira M, Ribeiro S, Ferreira N, Azevedo O, and Lourenço A

Abstract

An 18-year-old male presented with syncope during a training break. Post-syncope, he developed effort dyspnea, which he associated with the Pfizer-BioNTech COVID-19 vaccine received a week earlier. Electrocardiogram showed T inversion in V1-V3, III, and aVF, while 24-hour Holter monitoring revealed frequent ventricular premature beats. A transthoracic echocardiogram showed severe biventricular dilation and mild left ventricular (LV) dysfunction. Cardiac magnetic resonance (CMR) imaging confirmed these findings, showing moderate right ventricular (RV) systolic dysfunction with akinesia of the inferior and inferolateral walls. T2 hypersignal in the middle segment of the inferior inferior interventricular septum suggested myocardial edema. Extensive transmural late gadolinium enhancement was noted in the RV and LV walls. An implantable loop recorder was implanted. Three months later, the patient was admitted with palpitations, fever, and a positive SARS-CoV-2 test. Sustained ventricular tachycardia (VT) episodes were documented and managed with amiodarone and β-blockers. Follow-up CMR showed a slight improvement in LV ejection fraction and resolution of edema. A single-chamber implantable cardioverter-defibrillator (ICD) was implanted. Genetic testing for arrhythmogenic RV cardiomyopathy (ARVC) was negative, and family screening was normal. Two years later, pre-syncope episodes occurred, and ICD interrogation revealed nonsustained VT. The patient is awaiting VT ablation. This case highlights the diagnostic and therapeutic challenges of ARVC, particularly in differentiating it from myocarditis. The "hot-phase" presentation, vaccine association, and subsequent SARS-CoV-2 infection added complexity. CMR was crucial for diagnosis, and VT management required a combination of medical therapy and invasive procedures.

Published
2024
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111. Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy.

Author

Fontana M, Berk JL, Gillmore JD, Witteles RM, Grogan M, Drachman B, Damy T, Garcia-Pavia P, Taubel J, Solomon SD, Sheikh FH, Tahara N, González-Costello J, Tsujita K, Morbach C, Pozsonyi Z, Petrie MC, Delgado D, Van der Meer P, Jabbour A, Bondue A, Kim D, Azevedo O, Hvitfeldt Poulsen S, Yilmaz A, Jankowska EA, Algalarrondo V, Slugg A, Garg PP, Boyle KL, Yureneva E, Silliman N, Yang L, Chen J, Eraly SA, Vest J, and Maurer MS

Abstract

Background: Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive, fatal disease. Vutrisiran, a subcutaneously administered RNA interference therapeutic agent, inhibits the production of hepatic transthyretin., Methods: In this double-blind, randomized trial, we assigned patients with ATTR-CM in a 1:1 ratio to receive vutrisiran (25 mg) or placebo every 12 weeks for up to 36 months. The primary end point was a composite of death from any cause and recurrent cardiovascular events. Secondary end points included death from any cause, the change from baseline in the distance covered on the 6-minute walk test, and the change from baseline in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score. The efficacy end points were assessed in the overall population and in the monotherapy population (the patients who were not receiving tafamidis at baseline) and were tested hierarchically., Results: A total of 655 patients underwent randomization; 326 were assigned to receive vutrisiran and 329 to receive placebo. Vutrisiran treatment led to a lower risk of death from any cause and recurrent cardiovascular events than placebo (hazard ratio in the overall population, 0.72; 95% confidence interval [CI], 0.56 to 0.93; P = 0.01; hazard ratio in the monotherapy population, 0.67; 95% CI, 0.49 to 0.93; P = 0.02) and a lower risk of death from any cause through 42 months (hazard ratio in the overall population, 0.65; 95% CI, 0.46 to 0.90; P = 0.01). Among the patients in the overall population, 125 in the vutrisiran group and 159 in the placebo group had at least one primary end-point event. In the overall population, treatment with vutrisiran resulted in less of a decline in the distance covered on the 6-minute walk test than placebo (least-squares mean difference, 26.5 m; 95% CI, 13.4 to 39.6; P<0.001) and less of a decline in the KCCQ-OS score (least-squares mean difference, 5.8 points; 95% CI, 2.4 to 9.2; P<0.001). Similar benefits were observed in the monotherapy population. The incidence of adverse events was similar in the two groups (99% in the vutrisiran group and 98% in the placebo group); serious adverse events occurred in 62% of the patients in the vutrisiran group and in 67% of those in the placebo group., Conclusions: Among patients with ATTR-CM, treatment with vutrisiran led to a lower risk of death from any cause and cardiovascular events than placebo and preserved functional capacity and quality of life. (Funded by Alnylam Pharmaceuticals; HELIOS-B ClinicalTrials.gov number, NCT04153149.)., (Copyright © 2024 Massachusetts Medical Society.)

Published
2024
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112. Multi-marker DNA metabarcoding for precise species identification in ichthyoplankton samples.

Author

Ferreira AO, Azevedo OM, Barroso C, Duarte S, Egas C, Fontes JT, Ré P, Santos AMP, and Costa FO

Subjects
Animals, Electron Transport Complex IV genetics, Genetic Markers, Portugal, RNA, Ribosomal genetics, Biodiversity, Zooplankton genetics, Zooplankton classification, DNA Barcoding, Taxonomic methods, Fishes genetics, Fishes classification, RNA, Ribosomal, 16S genetics
Abstract

Ichthyoplankton monitoring is crucial for stock assessments, offering insights into spawning grounds, stock size, seasons, recruitment, and changes in regional ichthyofauna. This study evaluates the efficiency of multi-marker DNA metabarcoding using mitochondrial cytochrome c oxidase subunit I (COI), 12S rRNA and 16S rRNA gene markers, in comparison to morphology-based methods for fish species identification in ichthyoplankton samples. Two transects with four coastal distance categories were sampled along the southern coast of Portugal, being each sample divided for molecular and morphological analyses. A total of 76 fish species were identified by both approaches, with DNA metabarcoding overperforming morphology-75 versus 11 species-level identifications. Linking species-level DNA identifications with higher taxonomic morphological identifications resolved several uncertainties associated with traditional methods. Multi-marker DNA metabarcoding improved fish species detection by 20-36% compared to using a single marker/amplicon, and identified 38 species in common, reinforcing the validity of our results. PERMANOVA analysis revealed significant differences in species communities based on the primer set employed, transect location, and distance from the coast. Our findings underscore the potential of DNA metabarcoding to assess ichthyoplankton diversity and suggest that its integration into routine surveys could enhance the accuracy and comprehensiveness of fish stock assessments., (© 2024. The Author(s).)

Published
2024
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113. Renal and multisystem effectiveness of 3.9 years of migalastat in a global real-world cohort: Results from the followME Fabry Pathfinders registry.

Author

Hughes DA, Sunder-Plassmann G, Jovanovic A, Brand E, West ML, Bichet DG, Pisani A, Nowak A, Torra R, Khan A, Azevedo O, Lehman A, Linhart A, Rutecki J, Giuliano JD, Krusinska E, and Nordbeck P

Abstract

Fabry disease is a progressive, X-linked lysosomal disorder caused by reduced or absent α-galactosidase A activity due to GLA variants. The effects of migalastat were examined in a cohort of 125 Fabry patients with migalastat-amenable GLA variants in the followME Pathfinders registry (EUPAS20599), an ongoing, prospective, patient-focused registry evaluating outcomes for current Fabry disease treatments. We report annualised estimated glomerular filtration rate (eGFR) and Fabry-associated clinical events (FACEs) in a cohort of patients who had received ≥3 years of migalastat treatment in a real-world setting. As of August 2022, 125 patients (60% male) had a mean migalastat exposure of 3.9 years. At enrolment, median age was 58 years (males, 57; females, 60) with a mean eGFR of 83.7 mL/min/1.73 m 2 (n = 122; males, 83.7; females, 83.8) and a median left ventricular mass index of 115.1 g/m 2 (n = 61; males, 131.2; females, 98.0). Mean (95% confidence interval) eGFR annualised rate of change in the overall cohort (n = 116) was -0.9 (-10.8, 9.9) mL/min/1.73 m 2 /year with a similar rate of change observed across patients with varying levels of kidney function at enrolment. Despite population age and baseline morbidity, 80% of patients did not experience a FACE during the mean 3.9 years of migalastat exposure. The incidence of renal, cardiac, and cerebrovascular events was 2.0, 83.2, and 4.1 events per 1000 patient-years, respectively. These data support a role of migalastat in preserving renal function and multisystem effectiveness during ≥3 years of migalastat treatment in this real-world Fabry population., (© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Published
2024
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114. Inflammation and Exosomes in Fabry Disease Pathogenesis.

Author

Coelho-Ribeiro B, Silva HG, Sampaio-Marques B, Fraga AG, Azevedo O, Pedrosa J, and Ludovico P

Subjects
Humans, Animals, Extracellular Vesicles metabolism, Fabry Disease genetics, Fabry Disease metabolism, Fabry Disease pathology, Inflammation pathology, Exosomes metabolism
Abstract

Fabry Disease (FD) is one of the most prevalent lysosomal storage disorders, resulting from mutations in the GLA gene located on the X chromosome. This genetic mutation triggers glo-botriaosylceramide (Gb-3) buildup within lysosomes, ultimately impairing cellular functions. Given the role of lysosomes in immune cell physiology, FD has been suggested to have a profound impact on immunological responses. During the past years, research has been focusing on this topic, and pooled evidence strengthens the hypothesis that Gb-3 accumulation potentiates the production of pro-inflammatory mediators, revealing the existence of an acute inflammatory process in FD that possibly develops to a chronic state due to stimulus persistency. In parallel, extracellular vesicles (EVs) have gained attention due to their function as intercellular communicators. Considering EVs' capacity to convey cargo from parent to distant cells, they emerge as potential inflammatory intermediaries capable of transporting cytokines and other immunomodulatory molecules. In this review, we revisit the evidence underlying the association between FD and altered immune responses and explore the potential of EVs to function as inflammatory vehicles.

Published
2024
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115. Transthyretin amyloid cardiomyopathy in severe aortic stenosis submitted to valve replacement: a multicenter study.

Author

Pereira T, Fernandes RM, Mata E, Azevedo O, Bento D, Jesus I, and Lourenço A

Subjects
Humans, Male, Female, Aged, Heart Valve Prosthesis Implantation methods, Aged, 80 and over, Severity of Illness Index, Echocardiography methods, Prealbumin metabolism, Prealbumin genetics, Prevalence, Aortic Valve Stenosis surgery, Aortic Valve Stenosis diagnosis, Cardiomyopathies etiology, Cardiomyopathies diagnosis, Amyloid Neuropathies, Familial complications, Amyloid Neuropathies, Familial surgery
Abstract

Aim: To evaluate the prevalence of TTR amyloid cardiomyopathy (ATTR-CM) in severe aortic stenosis (SAS) patients, and to determine the independent predictors of major adverse events (MAE). Patients & methods: 91 SAS patients >65 years with an interventricular septum thickness ≥12.5 mm were referred for aortic valve replacement (AVR). 99mTc-DPD scintigraphy was applied to diagnose ATTR-CM, in the absence of monoclonal protein. Results: ATTR-CM was found in 11%. 78% of patients underwent AVR, but only 2 had ATTR-CM. There were no significant differences in the composite of all cause-mortality or cardiovascular hospitalizations. Lower left ventricle ejection fraction and not performing AVR were independent predictors of MAE. Conclusion: Not performing AVR was an independent predictor of MAE, regardless the ATTR-CM diagnosis.

Published
2024
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117. Massive cholangiocarcinoma metastasis compressing the heart in silence.

Author

Pereira T, Cardoso AF, Cordeiro F, Azevedo O, and Lourenço A

Subjects
Humans, Bile Ducts, Intrahepatic pathology, Cholangiocarcinoma diagnostic imaging, Cholangiocarcinoma pathology, Cholangiocarcinoma secondary, Bile Duct Neoplasms diagnostic imaging, Bile Duct Neoplasms pathology
Abstract

Competing Interests: Conflict of interest: None declared.

Published
2022
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118. Genotype-phenotype correlations in hypertrophic cardiomyopathy: a multicenter study in Portugal and Spain of the TPM1 p.Arg21Leu variant.

Author

Lamounier Junior A, Guitián González A, Rodríguez Vilela A, Repáraz Andrade A, Rubio Alcaide Á, Berta Sousa A, Benito López C, Alonso García D, Fernández Ferro G, Cruz I, Cárdenas Reyes IJ, Salazar-Mendiguchía García J, Larrañaga-Moreira JM, Ochoa JP, Palomino-Doza J, de la Higuera Romero L, Nicolás Cicerchia M, Restrepo Córdoba MA, Peña-Peña ML, Noël Brögger M, Loureiro M, Mogollón Jiménez MV, Bilbao Quesada R, Franco Gutiérrez R, García Hernández S, Ripoll-Vera T, Fernández X, Azevedo O, García Pavía P, Lopes LR, Ortiz M, Brito D, Barriales-Villa R, and Monserrat Iglesias L

Subjects
Aged, Female, Genetic Association Studies, Humans, Male, Middle Aged, Mutation, Pedigree, Phenotype, Portugal epidemiology, Spain epidemiology, Cardiomyopathy, Hypertrophic diagnosis, Cardiomyopathy, Hypertrophic genetics, Tropomyosin genetics
Abstract

Introduction and Objectives: TPM1 is one of the main hypertrophic cardiomyopathy (HCM) genes. Clinical information on carriers is relatively scarce, limiting the interpretation of genetic findings in individual patients. Our aim was to establish genotype-phenotype correlations of the TPM1 p.Arg21Leu variant in a serie of pedigrees., Methods: TPM1 was evaluated by next-generation sequencing in 10 561 unrelated probands with inherited heart diseases. Familial genetic screening was performed by the Sanger method. We analyzed TPM1 p.Arg21Leu pedigrees for cosegregation, clinical characteristics, and outcomes. We also estimated the geographical distribution of the carrier families in Portugal and Spain., Results: The TPM1 p.Arg21Leu variant was identified in 25/4099 (0.61%) HCM-cases, and was absent in 6462 control individuals with other inherited cardiac phenotypes (P<.0001). In total, 83 carriers (31 probands) were identified. The combined LOD score for familial cosegregation was 3.95. The cumulative probability of diagnosis in carriers was 50% at the age of 50 years for males, and was 25% in female carriers. At the age of 70 years, 17% of males and 46% of female carriers were unaffected. Mean maximal left ventricular wall thickness was 21.4 ±7.65mm. Calculated HCM sudden death risk was low in 34 carriers (77.5%), intermediated in 8 (18%), and high in only 2 (4.5%). Survival free of cardiovascular death or heart transplant was 87.5% at 50 years. Six percent of carriers were homozygous and 18% had an additional variant. Family origin was concentrated in Galicia, Extremadura, and northern Portugal, suggesting a founder effect., Conclusions: TPM1 p.Arg21Leu is a pathogenic HCM variant associated with late-onset/incomplete penetrance and a generally favorable prognosis., (Copyright © 2021 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Published
2022
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